Can a cortisone (corticosteroid) shot cause an elevated white blood cell count in a general adult population?

Can a Cortisone Shot Cause Elevated White Blood Cell Count?

Yes, corticosteroid injections definitively cause elevated white blood cell counts, with increases peaking at 48 hours post-administration and potentially reaching up to 4.84 × 10⁹/L above baseline depending on the dose administered. 1

Mechanism and Magnitude of WBC Elevation

Corticosteroids cause leukocytosis primarily through decreased neutrophil adhesion to endothelial surfaces, mediated by reduced expression of adhesion molecules (Mac-1 and L-selectin) on neutrophils, which leads to demargination and increased circulating neutrophil counts. 2

Expected WBC Changes by Dose and Timing:

• Peak effect occurs at 48 hours after corticosteroid administration 1
• Low-dose steroids: Mean increase of 0.3 × 10⁹/L WBCs 1
• Medium-dose steroids: Mean increase of 1.7 × 10⁹/L WBCs 1
• High-dose steroids: Mean increase of 4.84 × 10⁹/L WBCs 1
• Overall mean increase: 2.4 × 10⁹/L WBCs across all doses at 48 hours 1

Differential Count Pattern:

The leukocytosis is characterized by: 3

• Predominant neutrophilia (polymorphonuclear cell increase)
• Concurrent monocytosis
• Eosinopenia
• Variable lymphopenia
• Percentage of neutrophils increases (e.g., from 54.6% to 58.1%) 2

Clinical Implications and Pitfalls

Distinguishing Steroid-Induced Leukocytosis from Infection:

Critical differentiating features: 3

• Steroid-induced leukocytosis: Rarely shows left shift (>6% band forms) or toxic granulation
• Infection-related leukocytosis: Typically shows left shift and toxic granulation

Important caveat: The number of white blood cells increases during acute phase response and is influenced by glucocorticoids (increased WBC), making interpretation challenging in inflammatory conditions. 4

Duration and Persistence:

• Leukocytosis can appear as early as the first day of treatment 3
• Maximal values typically reached within two weeks 3
• After peaking, WBC count decreases but does not return to pretreatment levels during continued therapy 3
• Even small doses administered over prolonged periods can induce extreme and persistent leukocytosis 3

Intra-articular Injections:

Following intra-articular corticosteroid injections (such as cortisone shots for joint pain), synovial fluid white blood cell counts increase, though this represents a local rather than systemic effect. 5 However, systemic absorption occurs and contributes to peripheral blood leukocytosis.

Practical Clinical Approach

When evaluating a patient with elevated WBC after cortisone injection:

1. Timing assessment: If WBC elevation occurs within 48 hours of injection and magnitude is ≤4.84 × 10⁹/L above baseline, attribute to steroid effect 1

2. Magnitude assessment: Increases larger than 4.84 × 10⁹/L suggest alternative causes requiring investigation 1

3. Differential examination: Check for left shift (>6% bands) and toxic granulation—their presence suggests infection rather than steroid effect 3

4. Dose consideration: After low-dose steroids, any significant increase should prompt evaluation for other causes of leukocytosis 1

5. Clinical context: In immunocompromised hosts or when infection is suspected, the presence of steroid-induced leukocytosis complicates diagnosis and requires heightened clinical vigilance 3